CN102219718A

CN102219718A - New synthesis method for p-tolunesulfonyl carbamide

Info

Publication number: CN102219718A
Application number: CN2010101495198A
Authority: CN
Inventors: 范纪超
Original assignee: JUYE JINLING BIO-TECHNOLOGY DEVELOPMENT CO LTD
Current assignee: JUYE JINLING BIO-TECHNOLOGY DEVELOPMENT CO LTD
Priority date: 2010-04-19
Filing date: 2010-04-19
Publication date: 2011-10-19

Abstract

The invention discloses a new synthesis method for p-tolune sulfonyl carbamide, which comprises the steps of adding p-toluenesulfonyl chloride into an urea and dichloroethane system for condensation reaction to generate the p-tolune sulfonyl carbamide, wherein the dichloroethane also can be substituted by one of toluene, dimethylbenzene, benzene, dichloromethane, chloroform and the like; and after completion of the condensation reaction, adding a sodium hydroxide solution to neutralize generated hydrogen chloride, dissociating and separating out the p-tolune sulfonyl carbamide, and filtering, thus obtaining the p-tolune sulfonyl carbamide. The yield achieves more than 90 percent, and the purity is more than or equal to 98 percent (with HPLC (high performance liquid chromatography)). Compared with the traditional method, the method has the advantages of omitting a raw material: aqueous ammonia, improving operation environment, avoiding generation of a byproduct: ammonium chloride, being high in product yield, good in quality, low in cost and high in popularization and application values.

Description

A kind of new synthetic method of tolylsulfonylurea

Affiliated technical field

The present invention relates to a kind of new synthetic method of tolylsulfonylurea, belong to the field of chemical synthesis.

Background technology

Tolylsulfonylurea is the raw material of synthetic antidiabetic drug tolbutamide, gliclazide; it normally makes para toluene sulfonamide at Tosyl chloride and ammoniacal liquor reaction; para toluene sulfonamide makes tolylsulfonylurea with urea, toluene reflux again under alkaline condition; this method reactions steps is many; yield is low, the raw material consumption amount is big, cost is high; and volatile owing to ammoniacal liquor when producing, be unfavorable for labour protection, and have by-product ammonium chloride to generate.

Summary of the invention

The objective of the invention is to seek a kind of novel method that can make Tosyl chloride and the synthetic tolylsulfonylurea of urea single step reaction.

Concrete grammar of the present invention is Tosyl chloride to be added to carry out condensation reaction in the organic system of being made up of urea, ethylene dichloride, ethylene dichloride also can be used a kind of replacement of toluene, dimethylbenzene, benzene, methylene dichloride, chloroform etc., generate tolylsulfonylurea, after condensation reaction is finished, add sodium hydroxide solution again, the hydrogenchloride that neutralization generates, tolylsulfonylurea is promptly free separates out, filter tolylsulfonylurea, yield reaches more than 90%, purity 〉=98% (HPLC).

Useful benefit of the present invention is: saves the ammoniacal liquor raw material than traditional method, improved operating environment, avoided the generation of by-product ammonium chloride, and the product yield height, quality is good, and cost is low, has highly application value.

Embodiment

Urea 39kg (0.65kmol) and ethylene dichloride 79kg (0.8kmol) are added in the condensation reaction jar, be warming up to 60 ℃, begin to drip ethylene dichloride 79kg (0.8kmol) solution of Tosyl chloride 95kg (0.5kmol), maintain the temperature at about 60～65 ℃, dropwise, be warming up to 70～72 ℃, insulation reaction 3.5 hours, be cooled to room temperature, add the aqueous sodium hydroxide solution for preparing, make reaction solution be neutral, ethylene dichloride is reclaimed in distillation then, till no ethylene dichloride steams, crystallisation by cooling, centrifugal, washing, get the slightly wet product of tolylsulfonylurea, slightly wet product can be directly used in refining.

The slightly wet product of tolylsulfonylurea, ethanol are added in the decoloring reaction jar, and heating makes its dissolving, adds activated carbon after the dissolving, insulation decolouring 5 minutes, press filtration is to crystallizer, and crystallisation by cooling filters, washing with alcohol, the dry tolylsulfonylurea 96.3kg that gets, yield is 90%.

Claims

1. the new synthetic method of a tolylsulfonylurea, raw material comprises Tosyl chloride, urea, ethylene dichloride, sodium hydroxide, water, it is characterized in that: Tosyl chloride is added to carries out condensation reaction in the organic phase of forming by urea, ethylene dichloride, generate tolylsulfonylurea, after condensation reaction is finished, add sodium hydroxide solution again, the hydrogenchloride that neutralization generates, tolylsulfonylurea is promptly free separates out, filter tolylsulfonylurea.

2. the new synthetic method of tolylsulfonylurea as claimed in claim 1, it is characterized in that: Tosyl chloride: urea: ethylene dichloride=1mol: 1～2mol: 2.6～4.0mol, preferably Tosyl chloride: urea: ethylene dichloride=1mol: 1.3mol: 3.2mol

3. the new synthetic method of tolylsulfonylurea as claimed in claim 1, it is characterized in that: the ethylene dichloride in the described organic phase also can be used a kind of replacement of toluene, dimethylbenzene, benzene, methylene dichloride, chloroform etc.;

4. the new synthetic method of tolylsulfonylurea as claimed in claim 1, it is characterized in that: described sodium hydroxide solution also can be potassium hydroxide solution, aqua calcis, sodium carbonate solution, sodium hydrogen carbonate solution, solution of potassium carbonate, potassium bicarbonate solution;

5. the new synthetic method of tolylsulfonylurea as claimed in claim 1, it is characterized in that: setting-up point is preferably in 60～72 ℃ at 0～150 ℃.